Genetic portrait of 23 Y-STR loci in the Naga tribes of Nagaland,India

To explore the genomic diversity and forensic characterization of Naga tribes, Nagaland, haplotypes for 23 Y-STR markers have been analyzed. In this study, 203 unrelated male individuals residing in the Northeast Indian state of Nagaland were selected. A total of 203 unique haplotypes were observed. The value of gene diversity (GD) and discrimination capacity (DC) was observed as 0.999999998927955 and 1 respectively. Forensic interest parameters viz., power of discrimination (PD), polymorphic information content (PIC), and matching probability (PM) were found to be 0.999999998695503, 0.999999976671191, and 1.3 × 10⁻⁹ respectively, for the studied population. Inter-population comparison study showed that the Naga tribes were found to have a distinct gene pool which is reflected in the neighbor-joining tree, principle coordinate analysis, and heat map. This is the first genetic study on Naga tribes based on 23 Y-STR markers. The Y chromosomal STR data will be useful for forensic DNA application and will enrich the existing Indian Y-STR database.

     

Co-infection of blood borne viruses in blood donors: A cross-sectional study from North India

Background

There are several studies on prevalence of individual infectious disease markers (mono-infection) in donors but none on prevalence of coinfection. Co-infection is significant as it leads to accelerated disease progression. We, therefore, evaluated the prevalence of co-infection among blood donors.

Harnessing the immune system to treat cancer

A major challenge for the immune system is to recognize and eliminate cells undergoing carcinogenesis. Immune defense against tumors is complex. It can be mediated early by the innate immune system (i.e., phagocytes, NK cells, NKT cells, cytokines, and complement proteins) and later by the adaptive immune system (i.e., B cells and T cells). The eight articles in this Review series on tumor immunology discuss the mechanisms underlying immune surveillance of tumors, the regulation of carcinogenesis by immune inflammatory mediators, current approaches to controlling tumor growth through immunotherapy, and novel targets of immunotherapy.     

Imidazopyridazine Inhibitors of Plasmodium falciparum Calcium-Dependent Protein Kinase 1 Also Target Cyclic GMP-Dependent Protein Kinase and Heat Shock Protein 90 To Kill the Parasite at Different Stages of Intracellular Development

Imidazopyridazine compounds are potent, ATP-competitive inhibitors of calcium-dependent protein kinase 1 (CDPK1) and of Plasmodium falciparum parasite growth in vitro. Here, we show that these compounds can be divided into two classes depending on the nature of the aromatic linker between the core and the R2 substituent group. Class 1 compounds have a pyrimidine linker and inhibit parasite growth at late schizogony, whereas class 2 compounds have a nonpyrimidine linker and inhibit growth in the trophozoite stage, indicating different modes of action for the two classes. The compounds also inhibited cyclic GMP (cGMP)-dependent protein kinase (PKG), and their potency against this enzyme was greatly reduced by substitution of the enzyme''s gatekeeper residue at the ATP binding site. The effectiveness of the class 1 compounds against a parasite line expressing the modified PKG was also substantially reduced, suggesting that these compounds kill the parasite primarily through inhibition of PKG rather than CDPK1. HSP90 was identified as a binding partner of class 2 compounds, and a representative compound bound to the ATP binding site in the N-terminal domain of HSP90. Reducing the size of the gatekeeper residue of CDPK1 enabled inhibition of the enzyme by bumped kinase inhibitors; however, a parasite line expressing the modified enzyme showed no change in sensitivity to these compounds. Taken together, these findings suggest that CDPK1 may not be a suitable target for further inhibitor development and that the primary mechanism through which the imidazopyridazines kill parasites is by inhibition of PKG or HSP90.     

Abnormalities in aortic properties: a potential link between left ventricular diastolic function and ventricular—aortic coupling in sickle cell disease

Left ventricular (LV) diastolic dysfunction in patients with sickle cell disease (SCD) is associated with increased mortality. However, its mechanisms are not well known, preventing the development of effective therapies. We hypothesized that patients with SCD have altered aortic properties despite normal blood pressure, which may contribute towards the development of diastolic dysfunction. We studied 31 stable adult patients with SCD (32 ± 7 years) and 12 healthy controls of similar age (29 ± 10 years) who underwent echocardiography and cardiovascular magnetic resonance (CMR) imaging on the same day. Echocardiographic measurements of mitral inflow and mitral annulus velocities were used to evaluate LV diastolic function. CMR imaging included standard LV function evaluation and myocardial tissue characterization as well as velocity-encoded images of the ascending aorta to measure aortic diastolic cross-sectional area, distensibility, as well as peaks and volumes of the global, forward and backward blood flow rate. Compared to controls, SCD patients had increased aortic diastolic area, global stroke volume, and both forward and backward flow, while aortic distensibility and peripheral blood pressure were similar. Furthermore, peak backward flow rate and volume were able to discriminate between patients with and without diastolic dysfunction. Our findings show that some aortic properties are altered in SCD patients and may be associated with diastolic dysfunction despite normal systolic blood pressure. If confirmed in larger studies, these aortic changes could be a novel therapeutic target to prevent or delay the development of LV diastolic dysfunction in SCD and thus potentially improve outcomes in these patients.     

Oral ulcer as an unusual feature of visceral leishmaniasis in an AIDS patient

Leishmaniasis, a globally prevalent parasitic disease, occurs in three forms, viz, visceral, cutaneous and mucocutaneous. It is transmitted by female Phlebotomus sandflies. Human immunodeficiency virus (HIV) infection is increasing worldwide and several reports indicate a rising trend of VL / HIV co-infection, modifying the traditional anthroponotic pattern of VL transmission. India is one of the countries having the largest burden of leishmaniasis; nevertheless, there are very few HIV / leishmania co-infection cases reported so far. We report a 35-year-old homemaker infected with the human immunodeficiency virus; she presented with an oral ulcer. The investigations carried out on her revealed that she was afflicted by visceral leishmaniasis and the oral ulceration was a part of the same. This is only the second such case from the Indian subcontinent and more significantly from a non-endemic area.